The pathogenic personality of gonococci (Gc) is largely determined by their surface constituents, including pili, Opa proteins, and lipooligosaccharide (LOS). Pili are critical for virulence, presumably because they adhere gonococci to the mucosal sites of infection; but these critical surface organelles change at high frequencies due to sequence changes in their expressed structural gene (pi/E). Expression of Opa or opacity-associated proteins of the outer membrane is a consistent feature of gonococci reisolated from male urethritis. A single strain has a repertoire of several different opa genes. The function of the Opa family of proteins is unclear except for their binding gonococci together and influencing both attachment and detachment of organisms from tissue culture cells in vitro. LOS structure influences the susceptibility of gonococci to killing by normal human sera. We are trying to define the generic mechanisms responsible for pilus structure variation and for "on/off" switching of opa genes. The degree of structural heterogeneity among the Opa repertoire of one strain has been evaluated by molecular cloning and sequencing all its opa elements. A topoisomerase (gyrase) of gonococci has been cloned, is being sequenced, and will be evaluated regarding its role in these pilin and Opa changes. LOS variation and sialylation (substitution of neuraminic acid residues) is being studied in terms of their affects on gonococcal surface properties and on the interactions of gonococci with host factors and cells.